Blood Purification in Patients with Sepsis Associated with Acute Kidney Injury: A Narrative Review.

Sepsis leads to organ dysfunction. Acute kidney injury, a common type of organ dysfunction, is associated with a high mortality rate in patients with sepsis. Kidney replacement therapy can correct the metabolic, electrolyte, and fluid imbalances caused by acute kidney injury. While this therapy can improve outcomes, evidence of its beneficial effects is lacking. Herein, we review the indications for blood purification therapy, including kidney replacement therapy, and the current knowledge regarding acute kidney injury in terms of renal and non-renal indications. While renal indications have been well-documented, indications for blood purification therapy in sepsis (non-renal indications) remain controversial. Excessive inflammation is an important factor in the development of sepsis; blood purification therapy has been shown to reduce inflammatory mediators and improve hemodynamic instability. Given the pathophysiology of sepsis, blood purification therapy may decrease mortality rates in these patients. Further trials are needed in order to establish the effectiveness of blood purification therapy for sepsis.

Use of broad-spectrum antimicrobials for more than 72 h and the detection of multidrug-resistant bacteria in Japanese intensive care units: a multicenter retrospective cohort study.

BACKGROUND: Large multicenter studies reporting on the association between the duration of broad-spectrum antimicrobial administration and the detection of multidrug-resistant (MDR) bacteria in the intensive care unit (ICU) are scarce. We evaluated the impact of broad-spectrum antimicrobial therapy for more than 72 h on the detection of MDR bacteria using the data from Japanese patients enrolled in the DIANA study. METHODS: We analyzed the data of ICU patients in the DIANA study (a multicenter international observational cohort study from Japan). Patients who received empirical antimicrobials were divided into a broad-spectrum antimicrobial group and a narrow-spectrum antimicrobial group, based on whether they received broad-spectrum antimicrobials for more or less than 72 h, respectively. Differences in patient characteristics, background of infectious diseases and empirical antimicrobial administration, and outcomes between the two groups were compared using the chi-square tests (Monte Carlo method) for categorical variables and the Mann-Whitney U-test for continuous variables. We also conducted a logistic regression analysis to investigate the factors associated with the detection of new MDR bacteria. RESULTS: A total of 254 patients from 31 Japanese ICUs were included in the analysis, of whom 159 (62.6%) were included in the broad-spectrum antimicrobial group and 95 (37.4%) were included in the narrow-spectrum antimicrobial group. The detection of new MDR bacteria was significantly higher in the broad-spectrum antimicrobial group (11.9% vs. 4.2%, p = 0.042). Logistic regression showed that broad-spectrum antimicrobial continuation for more than 72 h (OR [odds ratio] 3.09, p = 0.047) and cerebrovascular comorbidity on ICU admission (OR 2.91, p = 0.041) were associated with the detection of new MDR bacteria. CONCLUSIONS: Among Japanese ICU patients treated with empirical antimicrobials, broad-spectrum antimicrobial usage for more than 72 h was associated with the increased detection of new MDR bacteria. Antimicrobial stewardship programs in ICUs should discourage the prolonged use of empirical broad-spectrum antimicrobial therapy. Trial registration ClinicalTrials.gov, NCT02920463, Registered 30 September 2016, https://clinicaltrials.gov/ct2/show/NCT02920463.

Implementation of a rapid response system at an isolated radiotherapy facility through simulation training.

A rapid response system is required in a radiotherapy department for patients experiencing a critical event when access to an emergency department is poor due to geographic location and the patient is immobilised with a fixation device. We, therefore, rebuilt the response system and tested it through onsite simulations. A multidisciplinary core group was created and onsite simulations were conducted using a Plan-Do-Study-Act cycle. We identified the important characteristics of our facility, including its distance from the emergency department; the presence of many staff with little direct contact with patients; the treatment room environment and patient fixation with radiotherapy equipment. We also examined processes in each phase of the emergency response: detecting an emergency, calling the medical emergency team (MET), MET transportation to the site and on-site response and patient transportation to the emergency department. The protocol was modified, and equipment was updated. On-site simulations were held with and without explanation of the protocol and training scenario in advance. The time for the MET to arrive at the site during a 2017 simulation prior to the present project was 7 min, whereas the time to arrive after the first simulation session was shortened to 5 min and was then shortened further to 4 min in the second session, despite no prior explanation of the situation. A multidisciplinary project for emergency response with on-site simulations was conducted at an isolated radiation facility. A carefully planned emergency response is important not only in heavy ion therapy facilities but also in other departments and facilities that do not have easy access to hospital emergency departments.

Investigation of the optimal method of oxygen administration with simultaneous use of a surgical mask: a randomized control study.

PURPOSE: From the perspective of infection prevention during the Coronavirus disease 2019 (COVID-19) pandemic, a recommendation was made to use surgical masks after extubation in patients in the operating room. For compliance with this recommendation, anesthesiologists need to administer oxygen to the patient with an oxygen mask over the surgical mask. However, no studies have investigated whether this method allows good maintenance of oxygenation in patients. This study aimed to investigate which method of oxygen administration lends itself best to use with a surgical mask in terms of oxygenation. METHOD: We administered oxygen to the study subjects using all the following three methods in random order: an oxygen mask over or under a surgical mask and a nasal cannula under the surgical mask. Oxygenation was assessed using the oxygen reserve index (ORi) and end-tidal oxygen concentration (EtO2). RESULT: This study included 24 healthy volunteers. ORi values with administration of oxygen were higher in the order of a nasal cannula under the surgical mask, an oxygen mask under the surgical mask, and an oxygen mask over the surgical mask, with median values of 0.50, 0.48, and 0.43, respectively, and statistically significant differences between all groups (P < 0.001). EtO2 values were in the same order as ORi, with median values of 33.0%, 31.0%, and 25%, respectively, and statistically significant differences between all groups (P < 0.001). CONCLUSION: Wearing a surgical mask over the nasal cannula during oxygen administration is beneficial for oxygenation and might help prevent aerosol dispersal.

A novel system for teaching the in-plane vascular access technique: A simulation study.

ABSTRACT: The long-axis in-plane approach is amenable to ultrasound-guided central venous catheterization. However, the long-axis in-plane approach is considered difficult to learn because the needle should remain visible in the ultrasound beam during the procedure. We developed a novel competency-based modular system to acquire the skills for the long-axis in-plane approach. The purpose of this study is to evaluate the efficacy of this system.The study was approved by the local ethics committee. Participants performed ultrasound guided venous catheterization (pre-test), attended a 2-hour hands-on session with the teaching system and were then evaluated again (posttest). The teaching system is a simulator device consisting of an ultrasound probe, a simulated vessel, a needle, and an endoscope connected to a computer to visualize the image inside the simulated vessel. The success rate, visualization of the needle tip, and puncture accuracy were measured before and after training. The puncture accuracy was determined by evaluating the distance of the needle tip and needle shaft from the center of a simulated vessel. Primary outcomes were the success rate and the puncture accuracy. The secondary outcome was needle tip visualization. McNemar test was used to analyze success rate and needle tip visualization. Tukey test was used to analyze puncture accuracy. A P value <.05 was considered statistically significant.Forty-seven participants were enrolled in this study. The success rate was significantly increased (pre-test 79%, posttest 94%, P = .04). Ultrasound images from 42 participants were analyzed for puncture accuracy. Puncture accuracy significantly increased for needle tip distance (P = .03), but not shaft distance (P = .1). The needle tip visualization was significantly improved (P = .02).A novel competency-based teaching system was constructed in a step-by-step manner, which improved needle tip visualization and puncture accuracy, with a higher success rate.

Education program for prevention of outdoor accidents in middle-high aged trekkers: Monitoring of change in blood pressure and heart rate during exercise.

This is an observational study to evaluate cardiovascular parameters during an educational trekking program. The number of alpine accidents involving elderly trekkers has been increasing in developed countries in recent years. Many middle-high aged trekkers have potential cardiovascular risks of which they are unaware. More than 77% of trekkers involved in alpine accidents in Japan were aged >40 years. The most common cardiovascular conditions were stroke or heart attack while trekking at altitude. An alpine club conducted an 8-month education program with participants aged >40 years in the setting of a mountain-side town. Blood pressure and heart rate during outdoor exercise were monitored, and any other adverse effects were recorded. As a result, the cardiovascular parameters evaluated during the first and final trek presented a physiological and similar behavior, however, lower heart rate values were registered at the highest point of the route in the final trek (p < 0.05). The trend of these parameters was similar in males and females, and there was little correlation between the cardiovascular parameters and age. In conclusion, the lower heart rate values may indicate the higher risk awareness of trekkers while self-pacing the physical activity outdoors, which may indicate the positive effect of the education program in increasing the safety of such unsupervised activities.

Anesthetic management of a patient with situs inversus totalis undergoing coronary artery bypass grafting surgery: a case report.

BACKGROUND: Anesthetic management of coronary artery bypass grafting surgery (CABG) in a dextrocardia patient with situs inversus totalis is rarely encountered and seldom reported in the literature. CASE PRESENTATION: A 76-year-old Japanese female patient had been diagnosed with situs inversus totalis and coronary artery disease of 3 vessels, and she subsequently underwent elective CABG. A preoperative examination showed almost normal results. ECG showed right deviation with the normal lead position. In the operating room, ECG leads were applied in reverse. Pulmonary artery catheterization was performed via the left internal jugular vein. A transesophageal echocardiography (TEE) probe was introduced without difficulty. A different angle was needed to acquire the desired views because of her atypical anatomy. CONCLUSION: Careful perioperative evaluation, intraoperative management, and inspection of multiplane angle and probe adjustments in TEE are needed for anatomically abnormal patients.

A Case of Hypopituitarism Complicated by Non-Alcoholic Steatohepatitis and Severe Pulmonary Hypertension.

BACKGROUND Pulmonary arterial hypertension (PAH), which is caused by increased pulmonary artery pressure, results in right-heart failure and presents with shortness of breath, chest pain, and syncope. PAH has idiopathic, heritable, and drug/toxin causes and is accompanied by other conditions, including connective tissue disease, congenital heart disease, and portal hypertension. Rarely, portal hypertension causes a type of PAH called portopulmonary hypertension (POPH). Portal hypertension can be triggered by liver cirrhosis, which can result from non-alcoholic steatohepatitis (NASH), a metabolic syndrome caused by hypopituitarism. Although an association between hypopituitarism and POPH has been suggested, few reports have described this relationship. CASE REPORT A 43-year-old woman with hypopituitarism received hormone replacement therapy after partial hypothalamic resection at age 4 years. At age 32 years, she developed liver cirrhosis from NASH due to adult growth hormone (GH) deficiency. Despite restarting GH replacement therapy, she refused the required GH doses for economic reasons. She was hospitalized with abdominal pain and dyspnea and was found to have severe POPH. She received PAH-specific therapies, including endothelin receptor antagonist and prostacyclin analog. Pulmonary hypertension improved on day 3 of hospitalization while the cardiac index increased gradually. On day 12, her respiratory status rapidly worsened and percutaneous cardiopulmonary support was applied. On day 18, she died of multiple organ failure and disseminated intravascular coagulation despite intensive care management. CONCLUSIONS Severe PAH, particularly POPH, remains incurable despite the use of PAH-specific therapies and intensive care management. For hypopituitarism patients, careful observation, including of the cardiopulmonary system, can improve the prognosis after completing hormone replacement therapy.

COVID-19 with repeated positive test results for SARS-CoV-2 by PCR and then negative test results twice during intensive care: a case report.

BACKGROUND: Determining the infectiousness of patients with coronavirus disease 2019 is crucial for patient management. Medical staff usually refer to the results of reverse transcription polymerase chain reaction tests in conjunction with clinical symptoms and computed tomographic images. CASE PRESENTATION: We report a case of a 62-year-old Japanese man who twice had positive and negative test results by polymerase chain reaction for severe acute respiratory syndrome coronavirus 2 over 48 days of hospitalization, including in intensive care. His respiratory symptoms and computed tomographic imaging findings consistent with coronavirus disease 2019 improved following initial intensive care, and the result of his polymerase chain reaction test became negative 3 days before discharge from the intensive care unit. However, 4 days after this first negative result, his polymerase chain reaction test result was positive again, and another 4 days later, he had a negative result once more. Eight days after the second polymerase chain reaction negative test result, the patient's test result again became positive. Finally, his polymerase chain reaction results were negative 43 days after his first hospitalization. CONCLUSIONS: This case emphasizes the importance of repeat polymerase chain reaction testing and diagnosis based on multiple criteria, including clinical symptoms and computed tomographic imaging findings. Clinical staff should consider that a negative result by polymerase chain reaction does not necessarily certify complete coronavirus disease 2019 recovery.

Improvement of Severe COVID-19 in an Elderly Man by Sequential Use of Antiviral Drugs.

Although a variety of existing drugs are being tested for patients with coronavirus disease 2019 (COVID-19), no efficacious treatment has been found so far, particularly for severe cases. We report successful recovery in an elderly patient with severe pneumonia requiring mechanical ventilation and extracorporeal membrane oxygenation (ECMO). Despite administration of multiple antiviral drugs, including lopinavir/ritonavir, chloroquine, and favipiravir, the patient's condition did not improve. However, after administration of another antiviral drug, remdesivir, we were able to terminate invasive interventions, including ECMO, and subsequently obtained negative polymerase chain reaction results. Although further validation is needed, remdesivir might be effective in treating COVID-19.

Comparison of four documents describing adrenaline purification, and the work of three important scientists, Keizo Uenaka, Nagai Nagayoshi and Jokichi Takamine.

The name of Keizo Uenaka has not been documented in textbooks. However, Uenaka was the scientist who worked on ephedrine and played a practical role in the purification and crystallization of adrenaline. His handwritten memorandum, "On Adrenaline, Memorandum, July to December, 1900" is now stored in a Buddhist temple, Kyougyou-ji in Nashio, Japan. In the present report, we compared Uenaka's original description and Jokichi Takamine's published scientific reports, and examined how each statement in four documents are related to each other in terms of successful adrenaline crystallization. Uenaka's memorandum contained precise procedures and experimental tips for successful purification. The experimental steps were considered to transcribed in the first published document in The American Journal of Pharmacy by Takamine in 1901, and summarized in another document in ``Journal of Physiology'' in 1901. A Japanese version was published in ``Yakugakuzasshi'' in 1903 by translating the English paper in the American Journal of Pharmacy published in 1901. Reading Uenaka's memorandum, we realized that he tirelessly and diligently undertook routine experiments that to some of us might seem boring and laborious. Although the name of Uenaka is not globally well known, he was the main scientist who did the actual work of purifying adrenaline.

Hemodynamically adjusted infrahepatic inferior venous cava clamping can reduce postoperative deterioration in renal function: a retrospective observational study.

PURPOSE: Infrahepatic inferior vena cava (IIVC) clamping is beneficial for reducing the amount of bleeding during hepatic surgery, although the associated systemic circulatory deterioration is noticeable. The relationship between changes in the degree of IIVC clamping and postoperative renal function was retrospectively evaluated. METHODS: A total of 59 patients who underwent elective hepatic surgery with surgical IIVC clamping in the two years were analyzed. In 2016, constant 80% clamping of the IIVC was performed (29 cases), and in 2017, hemodynamically adjusted IIVC clamping was performed (30 cases). Intraoperative parameters, including total blood loss and number of blood transfusions, were examined. The use of each vasoactive agents was analyzed. Renal function in the acute postoperative phase was evaluated using serum creatinine (Cr) and estimated glomerular filtration rate (eGFR) values. RESULTS: Comparison of the two groups showed that bolus doses of both ephedrine and phenylephrine were significantly higher in the 2016 group (P = 0.0221, 0.0017). Continuous doses of dopamine were significantly higher in the 2016 group, while those of noradrenaline were not. Postoperative serum Cr levels relative to baseline (%) were significantly higher in the 2016 group immediately after surgery and on postoperative day (POD) 1 (P = 0.0143, 0.0012). Postoperative eGFR relative to baseline (%) was significantly higher in the 2016 group immediately postoperatively and on PODs 1 and 2 (P = 0.0042, 0.0003, 0.0382). CONCLUSION: Hemodynamically adjustable IIVC clamping might be superior to uniformly fixed clamping in preserving renal function without compromising the desired effect on hemostasis.

Reduction of Arterial Oxygen Saturation Among Rescuers During Cardiopulmonary Resuscitation in a Hypobaric Hypoxic Environment.

We experienced a case involving prolonged cardiopulmonary resuscitation (CPR) during cardiac arrest on Mt. Fuji (3776 m), demanding lengthy exertion by the rescuers performing CPR. Considering the effects of exertion on the rescuers, we examined their percutaneous arterial oxygen saturation during simulated CPR and compared the effects of compression-only and conventional CPR at 3700 m above sea level. The effects of CPR on the physical condition of rescuers were examined at the summit of Mt. Fuji: three rescue staff equipped with pulse-oximeters performed CPR with or without breaths using a CPR mannequin. At 3700 m, the rescuers' heart rate increased during CPR regardless of the presence or absence of rescue breathing. Percutaneous arterial oxygen saturation measured in such an environment was reduced only when CPR without rescue breathing was performed. Scores on the Borg scale, a subjective score of fatigue, after CPR in a 3700 m environment were 13 to 15 of 20 (somewhat hard to hard). Performing CPR at high altitude exerts a significant physical effect upon the condition of rescuers. Compression-only CPR at high altitude may cause a deterioration in rescuer oxygenation, whereas CPR with rescue breathing might ameliorate such deterioration.

A novel prediction equation of resting energy expenditure for Japanese septic patients.

Estimating nutrient consumption and administering appropriate nutritional therapy is essential for improving clinical outcomes in critically ill patients. Various equations, such as the Harris-Benedict equation, have been developed to estimate the required calories. Previous equations, however, targeted Westerners, whose physical characteristics are likely different from those of Asians. Hence, it is unclear whether these equations can be used for Asian patients. This study focused specifically on sepsis patients admitted to a single Japanese ICU, and aimed to develop novel equations to estimate their total energy expenditure. A total of 95 sepsis patients were included in this study. We measured resting energy expenditure (REE) by using indirect calorimetry, and created equations to calculate basal metabolic rate (BMR) using height, weight and age as variables. REE was predicted by multiplying BMR by the novel equation with the stress factor of 1.4. The prediction error of our novel equations were smaller than those of other conventional equations. We further confirmed the accuracy of our equations and that they were unaffected by patient age and disease severity by using data obtained from another patient group. The current study suggested that these equations might allow accurate estimation of the total energy expenditure and proper management of nutritional therapy in Asian sepsis patients.

Optical skill-assist device for ultrasound-guided vascular access: A preliminary simulation study.

Ultrasound-guided central venous catheterization may cause lethal mechanical complications intraoperatively. We developed a novel device to prevent such complications. It works as a needle guide to supplement the operator's skill. We evaluated the utility of this device in terms of the success rate and visualization of the needle tip while penetrating the target vessel using a simulator.This study was approved by the local ethics committee. The new device - an optical skill-assist device - has a slit and a mirror in the center. The operator can see the needle's reflection in the mirror through the slit and can thus ensure that the needle is directed in line with the ultrasound beam. Participants were recruited by placing an advertisement for a hands-on seminar on ultrasound-guided vascular access. They received hands-on training on the in-plane approach for 2 hours. Pre-test and post-test without the device and an additional test using the device were performed to evaluate the proficiency of ultrasound-guided vascular access. An endoscope inserted into the simulated vessel was used to detect the precise location of the needle tip in the vessel.The primary outcomes were the success rate of the procedure. The secondary outcome was visualization of the needle tip while penetrating the simulated vessel. The chi-squared test was used for comparing the success rate and needle tip visualization between the different tests. P < .05 was considered to indicate significant differences.Forty-two participants were enrolled in this study. The success rate did not increase after the simulation training (P = .1). Using the optical skill-assist device, the rate improved to 100%. There was a significant difference in success rate between the pre-test and additional test using the optical skill-assist device (P = .003). Needle tip visualization significantly improved with the use of the optical skill-assist device compared to the pre-test (P < .001) and post-test (P = .001).Simulation training improved participants' skill for ultrasound-guided vascular access, but the improvement depended on each participant. However, further, improvement was achieved with the use of the optical skill-assist device.The optical skill-assist device is useful for supplementing the operator's skill for ultrasound-guided central venous catheterization.

[Anesthetic Management of a Patient with Double Outlet Right Ventricle and Situs Inversus for Dilatation and Curettage of the Uterus].

A 30-year-old woman with a double outlet right ven- tricle and situs inversus was scheduled for dilatation and curettage of the uterus. We selected intravenous anesthesia which allowed spontaneous respiration, because of the short operation time and the low invasive surgery. We administered dexmedetomidine hydrochloride 1.1 µg · kg⁻¹ · hr⁻¹ and fentanyl (total amount 150 µg, three doses of 50 µg each) during operation. We accomplished anesthesia without appar- ent hemodynamic change or respiratory depression. We should select anesthetic method and anesthetic cautiously, considering patient's state.

Relationship between coronary artery stenosis and cardio-ankle vascular index (CAVI) in patients undergoing cardiovascular surgery.

BACKGROUND: The cardio-ankle vascular index (CAVI) was developed as an indicator of arterial wall stiffness, and it is less influenced by blood pressure (BP). We investigated the relationship between the CAVI and coronary artery disease (CAD), and evaluated the effects of rapid changes in BP induced by anesthetics on CAVI. MATERIALS AND METHODS: We measured the CAVI in 76 patients before and after the administration of anesthetics for elective cardiovascular surgery. The patients were assigned to groups with or without CAD (0VD). The CAD group was then divided into 3 subgroups based on the number of stenotic vessels (1VD, 2VD, and 3VD). We compared the CAVI between CAD and 0VD, and changes in BP during the induction of anesthesia. All data were analyzed using Stat View 5.0 software. RESULTS: Systolic BP significantly decreased from 145 ± 21 to 107 ± 20 mmHg, whereas CAVI was not altered after the administration of intravenous anesthetics. Changes in BP and in pre-anesthetic CAVI (pre-CAVI) did not correlate. The pre- and post-anesthetic values for the CAVI (post-CAVI) in the 0VD and CAD groups were 8.34 ± 1.01 and 8.44 ± 1.39, and 9.95 ± 1.22 and 10.12 ± 1.56, respectively. Both values were higher in the CAD, than in the 0VD group (P < 0.05). CONCLUSION: The CAVI is independent of BP and reproducible regardless of the induction of anesthesia and is significantly higher in patients with CAD. The CAVI might be able to predict atherosclerosis and coronary artery stenosis in patients undergoing cardiovascular surgery.

Effect of different blood glucose target levels on the incidence of hypoglycemia during insulin therapy in the intensive care unit.

BACKGROUND: Prior to 2003, the target blood glucose level at our institute was <200 mg/dL. This target was reassessed in 2004 and again in 2006 based on reports showing decreased mortality in patients with target glucose levels between 80 and 110 mg/dL and results from subsequent randomized controlled trials. The aim of the present study was to determine the incidence of hypoglycemia due to IIT. The primary endpoint of the study was the incidence of hypoglycemia, with secondary outcomes of morbidity and mortality in three different periods. METHODS: A total of 2038 patients admitted to the intensive care unit (ICU) were divided into three groups with different target blood glucose levels: Group H, <200 mg/dL; Group M, <150 mg/dL; and Group L, <120 mg/dL. The incidence of hypoglycemia and patient outcomes in the three groups were compared. RESULTS: The incidence of serious hypoglycemia (<40 mg/dL) in Groups H, M and L was 3.5%, 4.0%, and 5.4%, respectively; the incidence of moderate hypoglycemia (<60 mg/dL) was 9.4%, 11.7%, and 21.0% (P < 0.01), respectively. There were no significant differences among the groups in terms of days connected to the ventilator, length of ICU stay and ICU mortalities. CONCLUSIONS: The incidence of moderate hypoglycemia (<60 mg/dL) was significantly increased during the period when the target blood glucose level was <120 mg/dL. Changes in target blood glucose levels did not affect patient mortality.

Influence of hemodynamic variations on the pharmacokinetics of landiolol in patients undergoing cardiovascular surgery.

Although landiolol is useful in the emergency management of atrial fibrillation, atrial flutter, and tachycardia, as well as in perioperative arrhythmia control, the influence of hemodynamic changes on the pharmacokinetics of landiolol is unknown. We investigated the influence of hemodynamic variation and the following hepatocirculatory changes after systemic heparinization on the pharmacokinetics of landiolol in patients undergoing cardiovascular surgery under cardiopulmonary bypass. Cardiac output and cardiac index (CI) were continuously monitored in 19 patients using an arterial pressure-based cardiac output monitor. The middle and right hepatic venous blood flow indexes (mHVBFI and rHVBFI) were measured by transesophageal echocardiography, and hemodynamic data were collected at points (T1-T3) as follows: T1, before administration of heparin and after sternotomy; T2, just before systemic heparinization (300 U/kg); T3, 10 min after T2. The plasma concentration of landiolol was measured by HPLC at the same point. After administration of heparin, mean arterial blood pressure, CI, mHVBFI, and rHVBFI were significantly decreased (<0.05). Heart rate was not significantly changed. After systemic heparinization, the landiolol concentration was significantly decreased from 0.407±0.251 µg·mL(-1) to 0.232±0.207 µg·mL(-1) (<0.01). There was no significant difference between T1 and T2 (=0.88). In conclusion, the plasma concentration of landiolol was decreased by diminished CI due to systemic heparinization, but not affected by the change of hepatic blood flow.